Claims for Patent: 9,889,138

Summary for Patent: 9,889,138

Title:	Method for treating cancer
Abstract:	The present invention provides a method for treating or alleviating a symptom of a disorder, e.g., immune evasion, cancer-cell induced immune dysfunction, reduced immune response, lowered inflammation, decreased expression of a major histocompatibility complex (MHC), or cancer, characterized by aberrant, misregulated, or increased Enhancer of Zeste Homolog 2 (EZH2) activity in a cell or subject in need thereof by contacting the cell or administering to the subject a therapeutically effective amount of an EZH2 inhibitor.
Inventor(s):	Keilhack; Heike (Belmont, MA)
Assignee:	Epizyme, Inc. (Cambridge, MA)
Application Number:	15/211,792
Patent Claims:	1. A method comprising contacting a human cancer cell with an amount of an EZH2 inhibitor effective for increasing expression of a major histocompatibility complex (MHC) in the cancer cell, wherein (1) the cancer cell comprises a chromosomal translocation t(x;18)(p11.2;q11.2) that causes a SS18-SSX fusion gene; or (2) the function and/or expression of INI1 is reduced in the cancer cell; or (3) the cancer cell comprises aberrant, misregulated, or increased EZH2 activity. 2. The method of claim 1, wherein the cancer cell comprises aberrant, misregulated, or increased EZH2 activity. 3. The method of claim 1, wherein the cancer cell comprises a chromosomal translocation t(x;18)(p11.2;q11.2) that causes a SS18-SSX fusion gene. 4. The method of claim 1, wherein the function and/or expression of INI1 is reduced in the cancer cell. 5. The method of claim 1, wherein the EZH2 inhibitor is ##STR00045## ##STR00046## or a pharmaceutically acceptable salt thereof. 6. The method of claim 1, wherein the method further comprises contacting the cancer cell with a chemotherapeutic compound. 7. The method claim 6, wherein the chemotherapeutic compound is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, and a CTLA-4 inhibitor. 8. The method of claim 1, wherein the cancer cell is in a subject. 9. The method of claim 8, wherein the subject is a human. 10. The method claim 1, wherein the EZH2 inhibitor is ##STR00047## or a pharmaceutically acceptable salt thereof. 11. The method claim 1, wherein the EZH2 inhibitor is a pharmaceutically acceptable salt of ##STR00048## 12. The method claim 1, wherein the EZH2 inhibitor is ##STR00049## or a pharmaceutically acceptable salt thereof. 13. The method claim 1, wherein the EZH2 inhibitor is a pharmaceutically acceptable salt of ##STR00050## 14. The method claim 1, wherein the EZH2 inhibitor is ##STR00051## or a pharmaceutically acceptable salt thereof. 15. The method claim 1, wherein the EZH2 inhibitor is a pharmaceutically acceptable salt of ##STR00052## 16. The method claim 1, wherein the EZH2 inhibitor is ##STR00053## or a pharmaceutically acceptable salt thereof. 17. The method claim 1, wherein the EZH2 inhibitor is a pharmaceutically acceptable salt of ##STR00054## 18. The method claim 1, wherein the EZH2 inhibitor is ##STR00055## or a pharmaceutically acceptable salt thereof. 19. The method claim 1, wherein the EZH2 inhibitor is a pharmaceutically acceptable salt of ##STR00056## 20. The method of claim 1, wherein the MEC is selected from the group consisting of HLA-A, HLA B, HLA-C, HLA DM alpha, HLA DM beta, HLA-DO alpha, HLA DO beta 1, HLA DP alpha 1, HLA DP beta 1, HLA DR alpha, HLA-DR beta 1, HLA-DR beta 3, HLA DR beta 4, HLA E, HLA F, HLA G, HLA K, and HLA L. 21. The method of claim 10, wherein the MEC is selected from the group consisting of HLA-A, HLA B, HLA-C, HLA DM alpha, HLA DM beta, HLA-DO alpha, HLA DO beta 1, HLA DP alpha 1, HLA DP beta 1, HLA DR alpha, HLA-DR beta 1, HLA-DR beta 3, HLA DR beta 4, HLA E, HLA F, HLA G, HLA K, and HLA L. 22. The method of claim 10, wherein the method further comprises contacting the cancer cell with a chemotherapeutic compound. 23. The method claim 22, wherein the chemotherapeutic compound is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, and a CTLA-4 inhibitor. 24. The method claim 2, wherein the EZH2 inhibitor is ##STR00057## or a pharmaceutically acceptable salt thereof. 25. The method of claim 24, wherein the MEC is selected from the group consisting of HLA-A, HLA B, HLA-C, HLA DM alpha, HLA DM beta, HLA-DO alpha, HLA DO beta 1, HLA DP alpha 1, HLA DP beta 1, HLA DR alpha, HLA-DR beta 1, HLA-DR beta 3, HLA DR beta 4, HLA E, HLA F, HLA G, HLA K, and HLA L. 26. The method of claim 24, wherein the method further comprises contacting the cancer cell with a chemotherapeutic compound. 27. The method claim 26, wherein the chemotherapeutic compound is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, and a CTLA-4 inhibitor. 28. The method claim 3, wherein the EZH2 inhibitor is ##STR00058## or a pharmaceutically acceptable salt thereof. 29. The method of claim 28, wherein the MHC is selected from the group consisting of HLA-A, HLA B, HLA-C, HLA DM alpha, HLA DM beta, HLA-DO alpha, HLA DO beta 1, HLA DP alpha 1, HLA DP beta 1, HLA DR alpha, HLA-DR beta 1, HLA-DR beta 3, HLA DR beta 4, HLA E, HLA F, HLA G, HLA K, and HLA L. 30. The method of claim 28, wherein the method further comprises contacting the cancer cell with a chemotherapeutic compound. 31. The method of claim 30, wherein the chemotherapeutic compound is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, and a CTLA-4 inhibitor. 32. The method of claim 4, wherein the EZH2 inhibitor is ##STR00059## or a pharmaceutically acceptable salt thereof. 33. The method of claim 32, wherein the MHC is selected from the group consisting of HLA-A, HLA B, HLA-C, HLA DM alpha, HLA DM beta, HLA-DO alpha, HLA DO beta 1, HLA DP alpha 1, HLA DP beta 1, HLA DR alpha, HLA-DR beta 1, HLA-DR beta 3, HLA DR beta 4, HLA E, HLA F, HLA G, HLA K, and HLA L. 34. The method of claim 33, wherein the method further comprises contacting the cancer cell with a chemotherapeutic compound. 35. The method claim 34, wherein the chemotherapeutic compound is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, and a CTLA-4 inhibitor.